4ek9 - Revision history

OCA at 15:03, 14 March 2024

OCA — Thu, 14 Mar 2024 15:03:15 GMT

←Older revision		Revision as of 15:03, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.5Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [https://pdbe.org/4ek9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ek9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ek9 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [https://pdbe.org/4ek9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ek9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ek9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.	+	[https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	DOT1L is the human protein methyltransferase responsible for catalyzing the methylation of histone H3 on lysine 79 (H3K79). The ectopic activity of DOT1L, associated with the chromosomal translocation that is a universal hallmark of MLL-rearranged leukemia, is a required driver of leukemogenesis in this malignancy. Here, we present studies on the structure-activity relationship of aminonucleoside-based DOT1L inhibitors. Within this series, we find that improvements in target enzyme affinity and selectivity are driven entirely by diminution of the dissociation rate constant for the enzyme-inhibitor complex, leading to long residence times for the binary complex. The biochemical K(i) and residence times measured for these inhibitors correlate well with their effects on intracellular H3K79 methylation and MLL-rearranged leukemic cell killing. Crystallographic studies reveal a conformational adaptation mechanism associated with high-affinity inhibitor binding and prolonged residence time; these studies also suggest that conformational adaptation likewise plays a critical role in natural ligand interactions with the enzyme, hence, facilitating enzyme turnover. These results provide critical insights into the role of conformational adaptation in the enzymatic mechanism of catalysis and in pharmacologic intervention for DOT1L and other members of this enzyme class.	+
-		+
-	Conformational Adaptation Drives Potent, Selective and Durable Inhibition of the Human Protein Methyltransferase DOT1L.,Basavapathruni A, Jin L, Daigle SR, Majer CR, Therkelsen CA, Wigle TJ, Kuntz KW, Chesworth R, Pollock RM, Scott MP, Moyer MP, Richon VM, Copeland RA, Olhava EJ Chem Biol Drug Des. 2012 Sep 15. doi: 10.1111/cbdd.12050. PMID:22978415<ref>PMID:22978415</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4ek9" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]		*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 07:14, 28 September 2022

OCA — Wed, 28 Sep 2022 07:14:40 GMT

←Older revision		Revision as of 07:14, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of DOT1L in complex with EPZ000004==		==Crystal structure of DOT1L in complex with EPZ000004==
-	<StructureSection load='4ek9' size='340' side='right' caption='[[4ek9]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='4ek9' size='340' side='right'caption='[[4ek9]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qow\|3qow]], [[4ekg\|4ekg]], [[4eki\|4eki]]</td></tr>~~	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [https://pdbe.org/4ek9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ek9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ek9 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [~~http~~://pdbe.org/4ek9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ek9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ek9 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.	+	[[https://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Histone methyltransferase\|Histone methyltransferase]]	+	*[[Histone methyltransferase 3D structures\|Histone methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone-lysine N-methyltransferase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Jin, L]]	+	[[Category: Jin L]]
-	~~[[Category: Methyltransferase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 05:26, 5 August 2016

OCA — Fri, 05 Aug 2016 05:26:01 GMT

←Older revision		Revision as of 05:26, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of DOT1L in complex with EPZ000004==		==Crystal structure of DOT1L in complex with EPZ000004==
	<StructureSection load='4ek9' size='340' side='right' caption='[[4ek9]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4ek9' size='340' side='right' caption='[[4ek9]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qow\|3qow]], [[4ekg\|4ekg]], [[4eki\|4eki]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qow\|3qow]], [[4ekg\|4ekg]], [[4eki\|4eki]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ek9 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [http://pdbe.org/4ek9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ek9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ek9 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4ek9" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Histone-lysine N-methyltransferase]]		[[Category: Histone-lysine N-methyltransferase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Jin, L]]		[[Category: Jin, L]]
	[[Category: Methyltransferase]]		[[Category: Methyltransferase]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 16:07, 25 December 2014

OCA — Thu, 25 Dec 2014 16:07:22 GMT

←Older revision		Revision as of 16:07, 25 December 2014
Line 9:		Line 9:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ek9 PDBsum]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ek9 PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DOT1L_HUMAN DOT1L_HUMAN]] Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 14:36, 9 December 2014

OCA — Tue, 09 Dec 2014 14:36:13 GMT

←Older revision		Revision as of 14:36, 9 December 2014
Line 1:		Line 1:
-	[[~~Image:~~4ek9.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of DOT1L in complex with EPZ000004==
		+	<StructureSection load='4ek9' size='340' side='right' caption='[[4ek9]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ek9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EK9 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EP4:5-DEOXY-5-(DIMETHYLAMINO)ADENOSINE'>EP4</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qow\|3qow]], [[4ekg\|4ekg]], [[4eki\|4eki]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DOT1L, KIAA1814, KMT4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone-lysine_N-methyltransferase Histone-lysine N-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.43 2.1.1.43] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ek9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ek9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ek9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ek9 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	DOT1L is the human protein methyltransferase responsible for catalyzing the methylation of histone H3 on lysine 79 (H3K79). The ectopic activity of DOT1L, associated with the chromosomal translocation that is a universal hallmark of MLL-rearranged leukemia, is a required driver of leukemogenesis in this malignancy. Here, we present studies on the structure-activity relationship of aminonucleoside-based DOT1L inhibitors. Within this series, we find that improvements in target enzyme affinity and selectivity are driven entirely by diminution of the dissociation rate constant for the enzyme-inhibitor complex, leading to long residence times for the binary complex. The biochemical K(i) and residence times measured for these inhibitors correlate well with their effects on intracellular H3K79 methylation and MLL-rearranged leukemic cell killing. Crystallographic studies reveal a conformational adaptation mechanism associated with high-affinity inhibitor binding and prolonged residence time; these studies also suggest that conformational adaptation likewise plays a critical role in natural ligand interactions with the enzyme, hence, facilitating enzyme turnover. These results provide critical insights into the role of conformational adaptation in the enzymatic mechanism of catalysis and in pharmacologic intervention for DOT1L and other members of this enzyme class.

-	~~{{STRUCTURE_4ek9\| PDB=4ek9 \| SCENE= }}~~	+	Conformational Adaptation Drives Potent, Selective and Durable Inhibition of the Human Protein Methyltransferase DOT1L.,Basavapathruni A, Jin L, Daigle SR, Majer CR, Therkelsen CA, Wigle TJ, Kuntz KW, Chesworth R, Pollock RM, Scott MP, Moyer MP, Richon VM, Copeland RA, Olhava EJ Chem Biol Drug Des. 2012 Sep 15. doi: 10.1111/cbdd.12050. PMID:22978415<ref>PMID:22978415</ref>

-	~~===Crystal structure~~ of ~~DOT1L in complex with EPZ000004===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

-	~~{{ABSTRACT_PUBMED_22978415}}~~	+	==See Also==
-		+	*[[Histone methyltransferase\|Histone methyltransferase]]
-	==~~About this Structure~~==	+	== References ==
-	[[~~4ek9~~]] ~~is a 1 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA].~~	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Histone-lysine N-methyltransferase]]		[[Category: Histone-lysine N-methyltransferase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Jin, L.]]	+	[[Category: Jin, L]]
	[[Category: Methyltransferase]]		[[Category: Methyltransferase]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 08:29, 9 January 2013

OCA — Wed, 09 Jan 2013 08:29:38 GMT

←Older revision		Revision as of 08:29, 9 January 2013
Line 1:		Line 1:
-	[[Image:4ek9.~~jpg~~\|left\|200px]]	+	[[Image:4ek9.png\|left\|200px]]

	{{STRUCTURE_4ek9\| PDB=4ek9 \| SCENE= }}		{{STRUCTURE_4ek9\| PDB=4ek9 \| SCENE= }}

OCA at 06:57, 17 October 2012

OCA — Wed, 17 Oct 2012 06:57:49 GMT

←Older revision		Revision as of 06:57, 17 October 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4ek9.jpg\|left\|200px]]

-	~~The entry~~ 4ek9 ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4ek9\| PDB=4ek9 \| SCENE= }}

-	~~Authors: Jin, L.~~	+	===Crystal structure of DOT1L in complex with EPZ000004===

-	~~Description: Crystal~~ structure ~~of DOT1L in complex~~ with ~~EPZ000004~~	+	{{ABSTRACT_PUBMED_22978415}}
		+
		+	==About this Structure==
		+	[[4ek9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EK9 OCA].
		+	[[Category: Histone-lysine N-methyltransferase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Jin, L.]]
		+	[[Category: Methyltransferase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:26, 30 May 2012

OCA — Wed, 30 May 2012 05:26:52 GMT

←Older revision		Revision as of 05:26, 30 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ek9 is ON HOLD	+	The entry 4ek9 is ON HOLD until Paper Publication

	Authors: Jin, L.		Authors: Jin, L.

	Description: Crystal structure of DOT1L in complex with EPZ000004		Description: Crystal structure of DOT1L in complex with EPZ000004

OCA: Protected "4ek9" [edit=sysop:move=sysop]

OCA — Wed, 18 Apr 2012 07:33:29 GMT

Protected "4ek9" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:33, 18 April 2012

OCA: New page: '''Unreleased structure''' The entry 4ek9 is ON HOLD Authors: Jin, L. Description: Crystal structure of DOT1L in complex with EPZ000004

OCA — Wed, 18 Apr 2012 07:33:28 GMT

New page: '''Unreleased structure''' The entry 4ek9 is ON HOLD Authors: Jin, L. Description: Crystal structure of DOT1L in complex with EPZ000004

New page

'''Unreleased structure'''

The entry 4ek9 is ON HOLD

Authors: Jin, L.

Description: Crystal structure of DOT1L in complex with EPZ000004